ABSTRACT
BACKGROUND: Brain injury can be induced by repeated high positive acceleration ( + Gz) exposure, but the mechanism was still unclear.OBJECTIVE: To investigate the role of apoptosis in higher + Gz exposures induced brain injury by observing the changes of mRNA expression of bcl-2,bax, p53, and interleukin-1β(IL-1β) hydroxylase in rat brain.DESIGN: Randomized control experimental study based on experimental SD rat model.SETTING: Aviation medicine research center of a hospital.MATERIALS: Twenty-six healthy male SD rats, weighed from 180 to 220 g,were randomly divided into control group(4 rats) and + Gz exposure group (22 rats).INTERVENTIONS: Rats were fixed on the rotating arm of animal centrifuger with their heads towards axis. Rats in + Gz exposure group were exposed to + 14 Gz for three times, each for 45 seconds with 30 minutes interval in between. Rats in control group were subject to the same experiment in + 1 Gz. The rat brains were taken 30 minutes, 6 hours, 24 hours and 48 hours after the last centrifuge run, and then fixed and embedded. Changes of bcl-2, bax, p53, and IL-1β hydroxylasein mRNA expressions in rat brain were measured with semi-quantitative reverse transcription polymerase chain reaction(RT-PCR) . Apoptotic cells were detected by terminal deoxynucleotide(correction of deoxynuleotide) transferase-mediated dUTP nick end labeling(TUNEL) technique.MAIN OUTCOME MEASURES: The changes of bcl-2, bax, p53, and IL-1 β hydroxyalse mRNA expressions at each time points.RESULTS: After repeated + Gz exposures for 6 hours, bcl-2 mRNA expression in rat brain tissue(0. 32 ± 0. 08) was found significantly lower than in control group(0. 69 ± 0. 15), while mRNA expressions of bax, p53, and interleukin-1β converting enzyme(ICE) 0.55 ±0. 09, 0. 48 ±0. 12, 0.79 ±0. 12were significantly higher than in control group 0.33 ±0. 09, 0. 31 ±0.05,0.51 ± 0.09 ( P ＜ 0. 01 ) . After 24 hours of exposure, mRNA expression of bcl-2 in rat brain tissue (0. 28 ± 0.05) was significantly lower than in control group, while the mRNA expressions of bax, p53, and ICE 0.61 ±0. 15,0.54 ± 0. 07, 0. 84 ± 0. 15 were significantly higher than in control group ( P ＜ 0.01); but the difference of brain bcl-2, bax, p53 and ICE mRNA expressions had no statistical significance when exposed for 0.5 hour and 48 hours( P ＞ 0.05). Partly apoptotic cells were observed at exposure for 6 hours and 24 hours.CONCLUSION: Changes of bcl-2, bax, p53 and ICE mRNA expressions, as well as apoptosis in rats brain can be induced by repeated + Gz exposures and may be involved in the molecular mechanisms of brain injury.
ABSTRACT
The purpose of this study is to observe the changes in gene expressions of bcl 2, bax, p53 and interleukin 1? converting enzyme (ICE) in the cerebral tissue of rat exposed to repeated +Gz, and to explore the pathogenetic role of apoptosis in brain damage induced by repeated +Gz exposures. The expression levels of bcl 2, bax, p53 and ICE in cerebral tissue of rats exposed to repeated +Gz were measured by semi quantitative reverse transcription polymerase chain reaction (RT PCR), and the apoptotic cells in brain tissue were detected by terminal deoxynuleotidyl transferase mediated dUTP nick end labeling technique. The results showed that the bcl 2 expression levels in the brain 6h and 24h after repeated +Gz exposures were significantly lower than those of control group, whereas the bax, p53 and ICE expression levels in the brains tissue 6h and 24h after repeated +Gz exposures were significantly higher than those of control group. Apoptotic cells could be observed in cerebral cortex, CA1 subregion of hippocampus and striatum at 6h and 24h after repeated +Gz exposures. It is suggested that the changes in bcl 2, bax, p53 and ICE expressions in rat brain can be induced by repeated +Gz exposures and apoptosis might be one of the molecular mechanisms of brain damage induced by repeated +Gz exposures